Longitudinal mapping of protective CD4+ T cell responses against HCV: analysis of fluctuating dominant and subdominant HLA-DR11 restricted epitopes.
Cellular immunity plays an important role in the control of persistent virus infections such as hepatitis C virus (HCV). Antiviral CD4(+) T cell responses have been shown to accompany resolution of acute disease and there is also a consistent association between HLA Class II genes, notably HLADRB1*1...
| Հիմնական հեղինակներ: | , , , , , |
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| Ձևաչափ: | Journal article |
| Լեզու: | English |
| Հրապարակվել է: |
2004
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| _version_ | 1826276719600861184 |
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| author | Harcourt, G Lucas, M Sheridan, I Barnes, E Phillips, R Klenerman, P |
| author_facet | Harcourt, G Lucas, M Sheridan, I Barnes, E Phillips, R Klenerman, P |
| author_sort | Harcourt, G |
| collection | OXFORD |
| description | Cellular immunity plays an important role in the control of persistent virus infections such as hepatitis C virus (HCV). Antiviral CD4(+) T cell responses have been shown to accompany resolution of acute disease and there is also a consistent association between HLA Class II genes, notably HLADRB1*1101 (and the closely linked HLADQB1*0301) and disease resolution. We initially mapped longitudinal CD4(+) T cell responses in an individual after spontaneous resolution of acute HCV, and identified three HLA-DR11-restricted responses which vary in immunodominance over time. Functional assays and HLA Class II tetramer staining revealed one to be a response to a commonly recognized epitope, NS3(1248-1261), although cytokine capture assays showed these specific cells to be at a very low frequency. In this patient, and in others reported, this most frequently recognized HLA-DR11 restricted epitope is not immunodominant. We analysed whether sequence variability within and between genotypes might account for differences in recognition of HLA-DR11 restricted epitopes. We found that a limited number, including NS3(1248-1261), showed extreme sequence conservation. Within NS3, the ability of peptides to accept amino acid substitutions was clearly related to the structure of the protein. Overall the data provide a deeper understanding of the relationship between protein structure and variability of HLA-DR11 restricted peptides and may explain the apparent dominance of responses to NS3(1248-1261) across studies but not within an individual immune response. |
| first_indexed | 2024-03-06T23:18:07Z |
| format | Journal article |
| id | oxford-uuid:67d20277-adf1-4582-a24a-d3d262cc2ef6 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:18:07Z |
| publishDate | 2004 |
| record_format | dspace |
| spelling | oxford-uuid:67d20277-adf1-4582-a24a-d3d262cc2ef62022-03-26T18:40:52ZLongitudinal mapping of protective CD4+ T cell responses against HCV: analysis of fluctuating dominant and subdominant HLA-DR11 restricted epitopes.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:67d20277-adf1-4582-a24a-d3d262cc2ef6EnglishSymplectic Elements at Oxford2004Harcourt, GLucas, MSheridan, IBarnes, EPhillips, RKlenerman, PCellular immunity plays an important role in the control of persistent virus infections such as hepatitis C virus (HCV). Antiviral CD4(+) T cell responses have been shown to accompany resolution of acute disease and there is also a consistent association between HLA Class II genes, notably HLADRB1*1101 (and the closely linked HLADQB1*0301) and disease resolution. We initially mapped longitudinal CD4(+) T cell responses in an individual after spontaneous resolution of acute HCV, and identified three HLA-DR11-restricted responses which vary in immunodominance over time. Functional assays and HLA Class II tetramer staining revealed one to be a response to a commonly recognized epitope, NS3(1248-1261), although cytokine capture assays showed these specific cells to be at a very low frequency. In this patient, and in others reported, this most frequently recognized HLA-DR11 restricted epitope is not immunodominant. We analysed whether sequence variability within and between genotypes might account for differences in recognition of HLA-DR11 restricted epitopes. We found that a limited number, including NS3(1248-1261), showed extreme sequence conservation. Within NS3, the ability of peptides to accept amino acid substitutions was clearly related to the structure of the protein. Overall the data provide a deeper understanding of the relationship between protein structure and variability of HLA-DR11 restricted peptides and may explain the apparent dominance of responses to NS3(1248-1261) across studies but not within an individual immune response. |
| spellingShingle | Harcourt, G Lucas, M Sheridan, I Barnes, E Phillips, R Klenerman, P Longitudinal mapping of protective CD4+ T cell responses against HCV: analysis of fluctuating dominant and subdominant HLA-DR11 restricted epitopes. |
| title | Longitudinal mapping of protective CD4+ T cell responses against HCV: analysis of fluctuating dominant and subdominant HLA-DR11 restricted epitopes. |
| title_full | Longitudinal mapping of protective CD4+ T cell responses against HCV: analysis of fluctuating dominant and subdominant HLA-DR11 restricted epitopes. |
| title_fullStr | Longitudinal mapping of protective CD4+ T cell responses against HCV: analysis of fluctuating dominant and subdominant HLA-DR11 restricted epitopes. |
| title_full_unstemmed | Longitudinal mapping of protective CD4+ T cell responses against HCV: analysis of fluctuating dominant and subdominant HLA-DR11 restricted epitopes. |
| title_short | Longitudinal mapping of protective CD4+ T cell responses against HCV: analysis of fluctuating dominant and subdominant HLA-DR11 restricted epitopes. |
| title_sort | longitudinal mapping of protective cd4 t cell responses against hcv analysis of fluctuating dominant and subdominant hla dr11 restricted epitopes |
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